Various presynaptic receptors (dopamine, DA; prostaglandin, PG; muscarinic and nicotinic) have been observed to exert a profound influence on the release and/or synthesis of DA from neurons in the rat neostriatum. Activation of presynaptic DA, muscarinic and PG receptors inhibit DA release while presynaptic DA receptors also inhibit synthesis. Nicotinic receptors increase DA release. The interaction and relative importance of these various local regulating mechanisms will be studied using superfused slices and synaptosomes obtained from the striatum as well as other brain regions such as nucleus accumbens, frontal cortex and median eminence. Release of 3H-DA, newly taken up or newly synthesized from 3H-tyrosine will be measured following electrical stimulation or depolarizing agents. Tyrosine hydroxylase activity will be simultaneously measured as an index of synthesis. These studies will determine if there are differences in presynaptic vs. postsynaptic DA receptors, whether presynaptic receptors are dependent upon the type of synapse or tissue, the mechanism of action and physiological importance of the various types of presynaptic regulation. BIBLIOGRAPHIC REFERENCES: Perkins, N. A. and Westfall, T. C.: Modulation of dopamine release from rat medial basal hypothalamus. Fed. Proceed. 36, 382, 1977. Atuk, N. O. and Westfall, T.C.: Integrated concentrations of catecholamines in phaeocromocytoma. The Lancet. Jan. 29, 259, 1977.